There has been recent interest in the role of natural killer cell-mediated cytotoxicity (NKCC) in IBD. While increased NKCC of allogeneic colon cells has been demonstrated by peripheral blood lymphocytes from Inflammatory Bowel disease (IBD) patients, the successful isolation of NK-cells from human gut and their cytotoxicity against autologous gut epitherlial cells has yet to be described in non-IBD patients. Recently, interferon has been shown to activate NK-cells against known sensitive and previously resistant target cells. In our preliminary studies, we have used centrifugal-elutriation to separate functional NK-lymphocytes and viable autologous epithelial cells from one ulcerative colitis (UC) and three non-IBD colons. Using a single cell cytotoxic assay we have demonstrated unstimulated and interferon-activated NKCC by human gut lymphocytes against known NK sensitive targets (K562) and autologous colon epithelial cells. Furthermore, we have shown increased, interferon-unresponsive NKCC against K562 autologous epithelial targets in one UC gut. Our plans in this proposal, therefore, are to use elutriation and single cell assay techniques to quantitate the activity, kinetics and modulation by PGE2 and interferon of NKCC by gut lymphocytes against autologous gut epithelium from non-IBD, UC and Crohn's disease (CD) bowels. We plan to correlate NK-kinetics with disease type, disease activity, and medications. Our next goal is to use similar techniques to investigate NK-binding and killing by lymphocytes from involved and uninvolved Crohn's disease gut of autologous targets from both areas. Cell studies will be done with five to ten specimens of non-IBD, UC and CD bowel mucosa.